Self-Assembled Nanobodies as Selectively Targeted, Nanostructured, and Multivalent Materials
Por:
Sanchez-Garcia, L, Volta-Duran, E, Parlade, E, Mazzega, E, Sanchez-Chardi, A, Serna, N, Lopez-Laguna, H, Mitstorfer, M, Unzueta, U, Vazquez, E, Villaverde, A, de Marco, A
Publicada:
30 jun 2021
Ahead of Print:
1 jun 2021
Resumen:
Nanobodies represent valuable tools in advanced therapeutic strategies but their small size (similar to 2.5 x similar to 4 nm) and limited valence for interactions might pose restrictions for in vivo applications, especially regarding their modest capacity for multivalent and cooperative interaction. In this work, modular protein constructs have been designed, in which nanobodies are fused to protein domains to provide further functionalities and to favor oligomerization into stable self-assembled nanoparticles. The nanobody specificity for their targets is maintained in such supramolecular complexes. Also, their diameter around 70 nm and multivalent interactivity should favor binding and penetrability into target cells via solvent-exposed receptor. These concepts have been supported by unrelated nanobodies directed against the ricin toxin (A3C8) and the Her2 receptor (EM1), respectively, that were modified with the addition of a reporter protein and a hexa-histidine tag at the C-terminus that promotes self-assembling. The A3C8-based nanoparticles neutralize the ricin toxin efficiently, whereas the EM1-based nanoparticles enable to selective imaging Her2-positive cells. These findings support the excellent extracellular and intracellular functionality of nanobodies organized in form of oligomeric nanoscale assemblies.
Filiaciones:
Sanchez-Garcia, L:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08193, Spain
Volta-Duran, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08193, Spain
Parlade, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08193, Spain
Mazzega, E:
Univ Nova Gorica, Lab Environm & Life Sci, Nova Gorica 5000, Slovenia
Sanchez-Chardi, A:
Univ Autonoma Barcelona, Serv Microscopia, Barcelona 08193, Spain
Univ Barcelona, Fac Biol, Dept Biol Evolut Ecol & Ciencies Ambientals, Barcelona 08028, Spain
Serna, N:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08193, Spain
Lopez-Laguna, H:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08193, Spain
Mitstorfer, M:
Univ Nat Resources & Life Sci, Inst Biochem, Dept Chem, A-1190 Vienna, Austria
Unzueta, U:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08193, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona 08025, Spain
Vazquez, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08193, Spain
Villaverde, A:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Barcelona 08193, Spain
de Marco, A:
Univ Nova Gorica, Lab Environm & Life Sci, Nova Gorica 5000, Slovenia
Green Published, hybrid
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